DESCRIPTION: (Applicant's Abstract) Smoking marijuana is known to acutely impair aspects of human cognition, to acutely change global and regional cerebral blood flow (rCBF), and to cause more subtle but permanent cognitive dysfunction in long-term users. However, little is known about changes in the brain's cognitive functions that are caused by smoking marijuana. This project investigates acute rCBF changes and associated cognitive dysfunction caused by smoking marijuana in both occasional and chronic users of the substance. Positron Emission Tomography (PET) with [15O] water will be used to measure rCBF in volunteer subjects performing attention and memory tasks that previous research has shown to be acutely effected by smoking marijuana. High resolution magnetic resonance (MR) images will also be obtained for each subject. MR landmarks will be used to place co-registered PET images into stereotaxic coordinate space for image subtraction and statistical mapping analyses. Specific hypotheses will also be tested by measuring rCBF within regions of interest traced upon the MR image. The specific PET activation paradigms to be used are drawn from those that we have previously developed to investigate attention and memory. We therefore have knowledge of brain regions activated by these tasks in normals, and abnormal rCBF patterns observed in schizophrenic patients with cognitive impairment. An initial study using a double-blind design will provide basic quantitative information about the time course and localization of marijuana on rCBF. Two studies will then use a double-blind design with occasional users of marijuana performing attention and memory tasks during PET imaging. One further study will assess the acute effects of smoking marijuana versus placebo in individuals who are chronic users of marijuana to measure rCBF changes associated with the deficits in memory that our group has found in such individuals. Our general hypothesis is that smoking marijuana will attenuate the task-specific pattern of rCBF that is characteristic of normal cognitive function. That is, that areas of activation will be smaller in spatial extent and lower in magnitude following marijuana, in conjunction with poorer cognitive performance. We hypothesize that this attenuation will be significantly greater in long-term users of marijuana. More specific regional hypotheses will be tested for the attention and memory tasks. These studies will be the first to provide information about the brain mechanisms associated with the acute but severe cognitive impairment caused by smoking marijuana in casual users. It will also be the first study to provide information about whether the acute changes in rCBF and cognitive function caused by smoking marijuana become more severe following chronic use of this substance.